Current methods used to inactivate living pathogens in vaccine production involve the use of chemical agents such as formaldehyde or betapropiolactone to chemically modify the genetic material of the pathogen. However, there is substantial evidence that both of these agents are human and animal carcinogens. For example, studies in rats exposed to formaldehyde by inhalation have shown that formaldehyde induces squamous-cell carcinoma of the nasal cavity. Additionally, formaldehyde has been shown to be genotoxic in vitro and in vivo. Both genotoxicity and cytotoxicity play an important role in the carcinogenicity of formaldehyde.
Although the concentration of formaldehyde in vaccines is typically low (below 0.02%), this represents up to 50-100 micrograms of formaldehyde per injected dose in many vaccines (for example, Anthrax vaccine produced by Bioport Corp. contains 100 microgram/ml formaldehyde as a preservative) and poses a potential hazard due to the number of vaccinations a person receives over the course of a lifetime. Particularly dangerous is the amount of formaldehyde that is injected into infants and small children during the course of multiple routine childhood vaccinations. While the amount of formaldehyde in each vaccine dose is low, the combined amount can become substantial.
Similarly, betapropiolactone, which is used in the inactivation of rabies virus, can produce an immune complex-reaction when combined with other components of the rabies vaccine. Additionally, it has been shown to produce squamous cell carcinomas, lymphomas and hepatomas in mice.
Thus, there is a need to develop a low cost, nontoxic alternative to formaldehyde and betapropiolactone for the inactivation of live pathogens, such as viruses, bacteria and parasites. The methods disclosed herein address this need, and provide substantial benefits not previously described in the art.